Work in the Wisconsin Clinical Genetics Center (WCGC) includes: 1) Delineation of new birth defect syndromes, their cause, natural history, prognosis and treatment; 2) study of "known" birth defects to better delineate their phenotypic spectrum, pathogenesis and cause, and the means to detect carriers, and to detect affected individuals prenatally; 3) cytogenetic studies of new and known aneuploidy syndromes; 4) studies of genetic pleiotropy in man; 5) investigations of the nature of gene expression in tissues, organs and cells of individuals (expressivity), in individuals vis-a-vis their genotype (penetrance), and in generations vs. their genotypes (phenotrance), in skeletal dysplasias (achondroplasia, hypochondroplasia), malformation syndromes (Wiedemann-Beckwith syndrome, prune belly syndrome, etc.), and cancers (retinoblastoma, Wilms' tumor, carotid body tumors, multiple glomus tumors and multiple cutaneous leiomyomata; 6) studies of methods of numerical taxonomy in clinical studies and genetic nosology; 7) studies of prenatal diagnosis, the incidence of Down's syndrome and neural tube defects in Wisconsin; 8) studies of the prevalence of developmental disabilities in Burnett Co. and Dane Co. Wis.; 9) health and genealogical surveys of all of the Old Order Amish in Wis., Illinois, Iowa, Missouri and Minnesota; 10) total dissections of fetuses and infants with known (genetic) syndromes and experimental studies of pathogenesis of congenital malformations in aneuploid mice; 11) causal, nosological and empiric recurrence risk studies in severe MR -especially that associated with primary CNS malformations; 12) mutational and genetic analysis of the experimentally (EMS) induced phenomenon of unstable premutation in Drosophila; 13) interdisciplinary studies of phenotype, pathogenesis, cause, nosology and recurrence risk in skeletal dysplasias and human intersexuality; 14) studies of the effects on offspring of parental consanguinity in Wis. rural Catholics; 15) studies on the pathology, anatomy and genetic defects of aborted fetuses and stillborn infants; 16) studies of mucopolysaccharide metabolism and of lysosomal hydrolases in human mucopolysaccharidoses, mucolipidoses, and lipidoses; 17) biochemical, EM, and histochemical studies of many pigment mutations in mouse, mink, and man.